Phenyl isocyanate → N-phenyl-4-dimethylamino-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide

HRID 1250487Notes

Reaction equation

HRID 1250487 reaction equation
Br[C:2]1[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[C:4]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:3]=1.CCCCCC.[Li]CCCC.[C:33]1([N:39]=[C:40]=[O:41])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(OCC)C>[C:33]1([NH:39][C:40]([C:2]2[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[C:4]([O:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=3)[N:3]=2)=[O:41])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 7672Phenyl isocyanateHCID 8058HexaneHCID 212498292-Bromo-N,N-dimethyl-6-[3-(trifluoromethyl)phenoxy]pyridin-4-amineHCID 178418339Butyllithium

Product 1

HCID 15906597N-phenyl-4-dimethylamino-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

0.8 g (0.0022 mol) of 2-bromo-4-dimethylamino-6-{3-(trifluoromethyl)phenoxy} pyridine was dissolved in about 15 ml of diethyl ether. While cooling the solution in a dry ice-acetone bath in an argon atmosphere, 1.5 ml of a 1.6M-hexane solution of BuLi (0.0022×1.1 mol) was added to the solution, followed by stirring the solution for about 10 minutes. After 0.60 g (0.0022×2.3 mol) of phenyl isocyanate dissolved in about 5 ml of diethyl ether was added to the reaction solution, the solution was removed from the bath and stirred at room temperature for about 30 minutes. The reaction solution was mixed with about 5 ml of a 1.2N-aqueous hydrochloric acid solution, and then distributed in ethyl acetate-water, followed by washing with saturated sodium bicarbonate water and saturated brine. The organic phase of the obtained solution was dried with anhydrous sodium sulfate, concentrated and subjected to silica gel column chromatography (eluting solution: ethyl acetate/hexane) to separate a main fraction therefrom. The fraction was concentrated and then precipitated with hexane, thereby obtaining an aimed product.

Workup

  1. additionwas added to the solution
  2. additionwas added to the reaction solution
  3. customthe solution was removed from the bath
  4. stirringstirred at room temperature for about 30 minutes
  5. additionThe reaction solution was mixed with about 5 ml of a 1.2N-aqueous hydrochloric acid solution
  6. washby washing with saturated sodium bicarbonate water and saturated brine
  7. dry with materialThe organic phase of the obtained solution was dried with anhydrous sodium sulfate
  8. concentrationconcentrated
  9. washsubjected to silica gel column chromatography (eluting solution: ethyl acetate/hexane)
  10. customto separate a main fraction
  11. concentrationThe fraction was concentrated
  12. customprecipitated with hexane

Sources & evidence

ORD record
ord-1fd758a562f94a29a5df7388a3e79f8e
Source dataset
uspto-grants-2002_01
Patent number
US06339045B1

Reaction notes

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